Role of 5-HT2AR in prefrontal cortex activity and plasticity in social behavior

SACSON AGOSTINA; SANCHEZ SANDA ALDANA; COMAS MUTIS RG; GIACHERO MARCELO; CALFA GD; WEISSTAUB NOELIA

Congreso; XXXVIII Congreso anual de la Sociedad Argentina de Investigación en Neurociencias; 2023

Serotonergic signalling has shown to be a key player in the modulation of social behavior. Specifically, serotonin type 2A receptors (5-HT2AR), known to be involved in a variety of behaviors, have also been linked to social cognition through the pathophysiology of different psychiatric and neurodevelopmental disorders, and its role in the mechanism of action of so-called “prosocial” drugs. Our lab found that 5-HT2AR knockout (htr2a-/-) had reduced discrimination indexes in the three-chambers social interaction test (SI) compared to wild types (htr2a+/+) mice. By genetically restoring the expression of 5-HT2AR in the forebrain, mice reached discrimination indexes similar to htr2a+/+. To further analyse the role of cortical 5-HT2AR in social behaviors, we used c-fos immunohistochemistry to indirectly gauge SI neural activity. Considering the potential developmental role of 5-HT2AR, we analysed the impact of the lack of 5-HT2AR’s expression on prefrontal cortex structural plasticity by studying dendritic spines. Preliminary data showed lower spine density in htr2a-/- mice’s infralimbic prefrontal cortex, suggesting distinct structural plasticity. These findings suggest a possible role of 5-HT2AR in social behavior in adult mice that might be potentially tied to prefrontal cortex plasticity differences.